Ex vivo and in vivo gene transfer to the peritoneal membrane in a rat model

The efficacy of peritoneal dialysis (PD) depends on preserving the structural integrity and dialysing capacity of the peritoneal membrane. Membrane structure and function can change on PD, resulting in decreased membrane performance and possible discontinuation of PD as a treatment modality. We hypothesized that a gene therapy strategy might be an innovative and promising approach to maintaining membrane integrity and dialysing capacity in the PD population. We have characterized two methods of genetic modification of the peritoneal membrane in a rat model to test the feasibility of this approach. In ex vivo gene transfer, mesothelial cells are isolated from the peritoneal membrane, genetically modified in culture and subsequently re-implanted back onto the peritoneal membrane of syngeneic recipients. In in vivo gene transfer, genetic modification of the membrane is accomplished in situ through adenovirus-mediated delivery of the genetic material into the peritoneal cavity. The peritoneal membrane can be genetically modified to produce factors that may be of therapeutic value in maintaining the fibrinolytic balance in the peritoneal cavity, moderating peritoneal inflammation, and studying the development of peritoneal fibrosis. These models provide a basis for studying the contribution of specific molecules to peritoneal membrane physiology. Optimally, they will be paired with other PD-relevant model systems to understand peritoneal physiology, identify ways to prevent membrane damage, and maintain dialysing performance. While gene transfer can be used as a tool to understand the individual roles of factors or pathways in peritoneal membrane physiology, it can also be developed as a therapy platform for improving membrane characteristics and enhancing the therapy of peritoneal dialysis.